Injection drug users play a central role in the current epidemics of HIV infection and tuberculosis (TB) in the United States. However, important questions remain unanswered concerning the incidence and prevalence of Mycobacterium tuberculosis (MTB) infection and disease among drug users, its specific relationship to drug use, and the effectiveness and impact of standard TB control strategies (e.g., tuberculin screening, prophylaxis, and treatment) in drug-using populations. We propose a research project to address these questions, with three major categories of study: 1. Studies of MTB Infection and Disease Among Drug Users: To determine the incidence and prevalence of MTB infection and disease in several populations of drug users in Connecticut, in relation to demographic, social, clinical, and behavioral variables. We will describe the community epidemiology of MTB in New Haven, CT, by creating detailed maps of the spatial and temporal patterns of drug use, HIV, and MTB in the city (including molecular genetic analysis of MTB strains), and predict trends of MTB infection and disease in New Haven drug users over a 3-year period. 2. Studies of the Efficiency of MTB Screening and Prophylaxis as a Community Intervention Among Drug Users: To estimate the completeness of existing MTB skin-test screening and chemoprophylaxis programs for drug injectors in New Haven, by monitoring the number of MTB infections in drug injectors that are detected and prophylaxed, and using mathematical models to compare the results with the total estimated number of MTB-infected drug injectors in the city. We will also predict and determine the impact of MTB skin-test screening and prophyiaxis among drug injectors on the TB case rate in New Haven over a 3-year period. 3. Studies Identifying Barriers to Effective MTB Prophylaxis in Distinct Populations of Drug Users: To compare the effectiveness of different models for providing MTB chemoprophylaxis to drug users, studying barriers to adherence with medication regimens in different treatment settings, and identifying effective strategies for community-based TB control which could be implemented in other urban settings. This project brings together a strong, multidisciplinary group of investigators with long experience in conducting clinical and epidemiologic studies of TB and HIV infection among drug users. The setting of a small city with high rates of drug use, MTB, and HIV infection, a small network of closely linked clinical care providers and public health agencies, and the broad resources of a major academic institution, provide unique opportunities in New Haven for a multifaceted and community-wide research project examining critical and timely issues concerning TB in drug users and strategies for its control.